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Biomedical subjects

F Isnard

Publications and source records attributed to F Isnard.

71 records · Page 4Linked to original sources
PubMed1988

A new combination of two intercalating agents (mitoxantrone + daunomycin) in adult refractory acute leukemia: the DON protocol.

A combination of two intercalating agents, mitoxantrone and daunorubicin with vincristine (the DON regimen) was studied in 16 patients with refractory acute leukemia, including three patients with myeloblastic transformation of refractory anemia with excess of myeloblasts after the failure of first-line chemotherapy and one additional patient with AML relapsing while off therapy. All patients had been heavily pretreated prior to receiving the DON regimen, and all but two had previously received high-dose anthracyclines. Of the 17 patients, nine (53%) who achieved complete remissions (CR) had myeloblastic leukemia. The three patients with acute lymphocytic leukemia did not achieve CR. Cardiac toxicity occurred in two patients and contributed to death in one. These results in very poor risk leukemia suggest a possible synergism in the action of the two intercalating agents and absence of increased cardiotoxicity.

Adolescent↗
PubMed1987

[Physiopathological approach to pathological hyperlactatemia in the diabetic patient. Value of blood metformin].

Type B lactic acidosis, or pathological hyperlactatemia (PHL), is defined by an arterial lactate level greater than 5 mmol X l-1. It is a known and severe complication of diabetes mellitus treated with biguanide hypoglycaemic agents, particularly phenformin which was taken off the French pharmaceutical market in 1977. Metformin, which remains the only biguanide hypoglycaemic agent currently prescribed in France, may also lead to this complication. However it does so less frequently and mostly in the diabetic presenting with renal failure. A few well studied cases showed that PHL could be correlated with excessive metformin blood levels, i.e. a toxic mechanism. In order to find out whether this toxic mechanism was the real cause of PHL in diabetics treated with metformin, a systematic study of metformin blood levels was carried out in 20 such patients. They had all been admitted to a critical care unit presenting with PHL. The results of this study led us to distinguish between two groups of patients. The seven patients of the first group had high metformin blood levels (4.3 to 65.8 micrograms X l-1). In these, renal excretion or extrarenal dialysis lowered or normalized their hyperlactatemia, and six of the seven recovered from PHL. In the second group, with thirteen patients, metformin blood levels were within the normal therapeutic range (0.225 to 3 micrograms X l-1) for seven patients and close to zero for the other six. This second group received the same treatment as the first one. Only three patients recovered, the others all died.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗
PubMed1986

[Radiologic aspects of acute invasive pulmonary aspergillosis in 18 immunodepressed patients].

A retrospective study of 18 immunodepressed patients with acute invasive pulmonary aspergillosis enabled the radiologic picture of this increasingly frequent opportunist affection to be described, and different manifestations of the disease as a function of underlying conditions to be determined. Two groups could be distinguished: the first of patients with malignant blood diseases (n = 10) when the "aplasia" factor was dominant; the second of patients without blood diseases (n = 8) when the immunodepression was usually induced by a recent increase in corticoid therapy. Neutropenia was not a finding in any of these patients. The most frequent radiologic finding was single or multiple round excavating foci, these corresponding to zones of bronchopneumonia containing aspergillus filaments with central tissue necrosis forming the "target" lesion. The aplasia was distinguished by the multiplicity of lesions and their excavation following aplasia in the shape of a crescent due to sequestrum formation. Prognosis was related to severity of subjacent lesions. In the 2nd group, lesions could be single and nodular; prognosis was improved by the possibility of reducing immunodepression factors.

Acute Disease↗
PubMedDate not supplied

Treatment with metformin of non-diabetic men with hypertension, hypertriglyceridaemia and central fat distribution: the BIGPRO 1.2 trial.

BACKGROUND: In the BIGPRO 1 trial, one year of treatment with metformin in non-diabetic obese subjects with a central fat distribution had no significant effect on fasting plasma triglyceride concentration or on blood pressure despite a decrease in weight, fasting plasma insulin and glucose concentrations. To re-evaluate the effect of metformin on fasting triglyceride concentration and on blood pressure, the BIGPRO 1.2 trial included non-diabetic men (n=168) with a fasting plasma triglyceride concentration > or =1.7 and < or =6.5 mmol/l, high blood pressure (systolic > or =140 and < or =180 and/or diastolic > or =90 and < or =105 mmHg, or treatment for hypertension) and a waist-to-hip ratio > or =0.95. METHODS: A randomised double-blind trial comparing metformin treatment (850 mg bid) with placebo. RESULTS: Metformin had no significant effect either on blood pressure or plasma triglyceride concentration. In comparison with the placebo group, fasting plasma insulin (p<0.04), total cholesterol (p<0.05) and Apo B (p<0.008) concentrations decreased more in the metformin group in the BIGPRO 1. 2 trial, confirming most of the previous results of the BIGPRO 1 trial. Tissue plasminogen activator antigen concentration decreased significantly (p<0.01) only in the metformin group, but this was not significantly different from the placebo group (p<0.12); further, there were no significant differences in the change in plasminogen activator inhibitor 1. CONCLUSIONS: The consistency of the two BIGPRO trials supports the conclusion that metformin affects several cardiovascular risk factors favourably in non-diabetic subjects with a central fat distribution.

Adipose Tissue↗
PubMedDate not supplied

[Autologous bone marrow graft in the initial treatment of follicular lymphomas in young high risk subjects. A new therapeutic approach].

Low grade malignant follicular lymphoma is characterized by its slow course over many years. However, despite a median survival of 4 to 8 years the cure rate is lower than 10 percent and even nil for some authors. The best therapeutic approach of the disease is unknown, and many teams of oncologists are in favour of a more intense chemotherapy. We present a study of 10 patients selected for their young age and for the presence of detrimental prognostic factors (index 3 of Coiffier's classification in 8/10 patients). Nine patients received BCNU, cytosine arabinoside, etoposide and melphalan, followed by reinjection of autologous bone marrow purged in vitro by mafosfamide in the adjusted dose CFUGM LD 95. Eight of these 9 patients are in complete, unmaintained remission 15 to 43 months after the bone marrow transplantation (including 3 patients in a more than 2 years' remission). The 10th patient had autologous bone marrow transplantation in 1979; after treatment with heavy TACC chemotherapy followed by reinjection of unpurged bone marrow, he remained in complete remission for 9 years, then relapsed; he is now alive with a progressive tumour. Although the follow-up was relatively short for a particularly slow disease, this study shows that, owing to autologous bone marrow transplantation as early as the first complete remission, one of the heaviest types of chemotherapy can be delivered in patients with non-Hodgkin's lymphoma, unless precluded by toxicity. At the moment, this protocol is experimental and can be used only in young subjects at high risk. Further studies on larger series of patients and with a longer follow-up are needed to evaluate the effectiveness of this new type of treatment compared with conventional chemotherapies.

Adult↗
PubMedDate not supplied

Pharmcokinetics in healthy volunteers and patients of NAc-SDKP (seraspenide), a negative regulator of hematopoiesis.

NAc-SDKP is a peptide being tested as a bone marrow hematopoiesis protector in chemotherapy trials in cancer patients. We studied the pharmacokinetics of NAc-SDKP in six healthy human volunteers and in five patients undergoing chemotherapy. Plasma concentrations of NAc-SDKP were monitored using a specific enzyme immunoassay. Because NAc-SDKP is an endogenous compound, a preliminary study was undertaken to determine intra- and interday baseline variations in healthy subjects. The baseline value (range 1.7-3.2 nM) differed between subjects, but was constant over time. The influence of the route of administration was studied in six healthy volunteers with 128 nmol/kg given as a 12-hr intravenous infusion or as a single subcutaneous or intramuscular injection. After cessation of intravenous infusion in healthy volunteers, NAc-SDKP was characterized by a quick elimination phase, with a mean half-life of 4.5 min. The volume distribution was 117 ml/kg and the area under the curve was 117 nM hr. After subcutaneous and intramuscular administrations, peak plasma drug concentrations occurred at 0.26 and 0.28 hr, with Cmax values of 156 and 110 nM, respectively. The bioavailabilities determined after subcutaneous and intramuscular administrations were 100 and 81%, respectively. NAc-SDKP pharmacokinetics was studied in patients after intravenous infusion over 48 hr of a dose of between 51.3 and 513 nmol/kg. Area under the curve values increased proportionately with the dose. Mean clearance was lower in patients than in healthy volunteers: 524 vs. 1120 ml/hr/kg, respectively.

Adult↗
PubMedDate not supplied

Marked intra- and inter-patient variability of itraconazole steady state plasma concentrations.

Itraconazole is a new oral triazole antifungal agent that is effective against a wide range of fungal pathogens, including Aspergillus species. There has been a considerable increase in recent years in its use in prophylaxis of aspergillosis in neutropenic patients. A total of 74 trough concentrations of itraconazole+active metabolite were retrospectively analysed at steady state in 16 patients admitted to hospital for acute myeloid leukaemia (12) or malignant lymphoma (4). The minimum therapeutic concentration (itraconazole+hydroxyitraconazole = 1000 ng/ml) was never reached in 31 per cent of patients (5/16) and a constant efficient plasma concentration was obtained in only 19 per cent (3/16) with a daily regimen of 400-600 mg. The plasma levels of patients at the same daily dose differed up to 15-fold. This study confirms the pronounced inter-patient variability of unchanged itraconazole concentrations previously found in volunteers and patients. The plasma levels in six patients during successive chemotherapy treatments also varied greatly. Intra-individual differences were more accurately examined in six patients given 600 mg itraconazole/day during their first chemotherapy treatment. The trough plasma concentrations on day 15 and day 25 varied from -53 to +245 per cent. These results indicate that the plasma itraconazole concentration of neutropenic patients must be monitored to ensure that each individual is given a clinically effective dose.

Adult↗